Breaking the feed forward inflammatory cytokine loop in the tumor microenvironment of PDGFB-driven glioblastomas.
Breaking the feed forward inflammatory cytokine loop in the tumor microenvironment of PDGFB-driven glioblastomas.
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DOI：
10.1172/jci175127
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发表时间：
2023-11-15
影响因子：
15.9
通讯作者：
Hjelmeland, Anita B.
中科院分区：
文献类型：
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作者：
Miller, C. Ryan;Hjelmeland, Anita B.
胶质母细胞瘤（GBM）肿瘤相关巨噬细胞（tam）提供了一个主要的免疫细胞群，通过产生促炎因子，包括IL-1，促进生长和免疫抑制。在这一期的JCI中，Chen， Giotti及其同事研究了PDGFB表达和Nf1敲低驱动的GBM模型中免疫肿瘤微环境（TME）中ll1b的缺失。生存率仅在pdgfb驱动的GBM模型中得到改善，表明肿瘤细胞基因型影响免疫TME。TME中的IL-1β通过增加肿瘤源性NF-κB、单核细胞趋化剂的表达和增加骨髓源性髓样细胞（bmdm）的浸润来增加pdgfb驱动的GBM生长。相比之下，在nf1沉默的肿瘤中，由于NF-κB和单核细胞化学引诱剂的基础水平较高，以及BMDM和tam的浸润增加，IL-1β的需求不明显。值得注意的是，用抗il -1β或il - 1r1拮抗剂治疗pdgfb驱动的GBM小鼠延长了生存期。这些发现表明，有效的临床免疫治疗可能需要不同的靶向策略。
Glioblastoma (GBM) tumor-associated macrophages (TAMs) provide a major immune cell population contributing to growth and immunosuppression via the production of proinflammatory factors, including IL-1. In this issue of the JCI, Chen, Giotti, and colleagues investigated loss of ll1b in the immune tumor microenvironment (TME) in GBM models driven by PDGFB expression and Nf1 knockdown. Survival was only improved in PDGFB-driven GBM models, suggesting that tumor cell genotype influenced the immune TME. IL-1β in the TME increased PDGFB-driven GBM growth by increasing tumor-derived NF-κB, expression of monocyte chemoattractants, and increased infiltration of bone marrow–derived myeloid cells (BMDMs). In contrast, no requirement for IL-1β was evident in Nf1-silenced tumors due to high basal levels of NF-κB and monocyte chemoattractants and increased infiltration of BMDM and TAMs. Notably, treatment of mice bearing PDGFB-driven GBM with anti–IL-1β or an IL1R1 antagonist extended survival. These findings suggest that effective clinical immunotherapy may require differential targeting strategies.